A pathological diagnosis is performed by viewing a microscope glass specimen referred to as a preparation with a microscope. The microscope specimen, which is made of an organ, tissue and a cell collected from a patient, is obtained by thinly slicing a sample into a few micron thick and thereafter staining the same. A microscopic observation of the specimen supports the diagnosis of illness by a doctor, and is used to determine a future approach to treatment and a prognosis. Especially, an observation of immunohistochemical staining (IHC, also simply referred to as immunostaining) in the breast cancer is used to determine a future indication for endocrine therapy.
An effect indicator of the endocrine therapy in the breast cancer is determined by occupancy or the like of estrogen receptor (ER) or progesterone receptor (PgR) positive cells of which cell nucleus is stained in tumor cells in the tissue. A tumor diagnosis is performed by the microscopic observation of a hematoxylin-eosin stained (HE-stained) specimen of a tissue section. Also, the indication determination for the endocrine therapy is diagnosed by the microscopic observation of the tissue section specimen stained by the immunohistochemical staining.
Therefore, the indication determination for the endocrine therapy in the breast cancer is diagnosed according to a following procedure. First, a pathologist determines the tumor by the microscopic observation of the HE-stained tissue section specimen by using an HE-stained tissue section and an immunohistochemically-stained tissue section adjacent to each other. Subsequently, the tissue section specimen obtained by staining the tissue section adjacent to the HE-stained tissue section by the immunohistochemical staining is checked against a portion corresponding to the tumor portion determined by the HE-staining. Thereby, a tumor portion is distinguished in the immunohistochemically-stained tissue section specimen. Then, the distinguished tumor portion of the immunohistochemically-stained tissue section specimen is microscopically observed.
Although this pathological test is one of a test methods generally performed in current medical institutions, standardization of an examination method and an evaluation method of the immunohistochemical staining is not realized. Although an automatic staining device for staining the tissue section is widely used and the number of cases of the pathological tests increases in these years, the number of pathologists is overwhelmingly small.
The HE-staining is the most general staining in which the cell nucleus is stained in blue by hematoxylin and a cell cytoplasm and connective tissue are stained in pink by eosin. The tumor is diagnosed by the observation of the HE-staining. At that time, the tumor is determined by direct microscopic observation of a pathological slide by the pathologist. On the other hand, it is also performed that the pathological slide is imaged and converted into an electric image, the pathological image is displayed on a computer display, and the image is observed by the pathologist and determined. Also, an example of the support system for the tumor diagnosis is disclosed in the Patent Document 1 (Japanese Patent Publication (Tokkai) No. 2006-153742).
The immunohistochemical staining is a method of detecting a local existence of target protein in the cell and in the tissue by utilizing specific binding reaction, which is antigen antibody reaction. That is to say, this is a method of determining whether the tumor cell itself produces a tumor marker, and this stains a substance referred to as the tumor marker. In the immunohistochemical staining, a chromogenic substrate referred to as diaminobenzidine (DAB), which stains in brownish red, is used, and a method of producing a color by DAB and staining the nucleus by hematoxylin is widely used. Principal tests by the immunohistochemical staining include an ER test, a PgR test and a HER-2 test. In the ER test and the PgR test, expression of ER and PgR is evaluated by the immunohistochemical staining, and when ER and PgR are positive, almost all of the tumor cell nuclei are stained in brown.
There are some determining criteria of the ER test and the PgR test by the immunohistochemical staining, such as a criterion based on only a staining positive cell content rate and a criterion based on a combination of the staining positive cell content rate and staining intensity, and there are various cut off values (Non-Patent Document 1: Leyfield L J, Guputa D, Mooney E E, “Assessment of tissue estrogen and progesterone receptor levels: a survey of current practice, techniques, and quantitation method”, Blackwell Publishing, The Breast Journal, Volume 6, Number 3, May 2000, pp. 189-196 (8).)
Meanwhile, as the related art documents relating to the present invention, there are the Patent Document 2 (Japanese Patent Publication (Tokkai) No. 2002-282215), the Patent Document 3 (Japanese Patent Publication (Tokkaihei) No. 05-159056), the Patent Document 4 (Japanese Patent Publication (Tokkaihei) No. 06-94706), and the Patent Document 5 (Japanese Patent Publication (Tokuhyo) No. 2004-532410) in addition to the Patent Document 1 and the Non-patent Literature 1.
[Patent Document 1] Japanese Patent Publication (Tokkai) No. 2006-153742
[Patent Document 2] Japanese Patent Publication (Tokkai) No. 2002-282215
[Patent Document 3] Japanese Patent Publication (Tokkaihei) No. 05-159056
[Patent Document 4] Japanese Patent Publication (Tokkaihei) No. 06-94706
[Patent Document 5] Japanese Patent Publication (Tokuhyo) No. 2004-532410
[Non-patent Literature 1] Leyfield L J, Guputa D, Mooney E E, “Assessment of tissue estrogen and progesterone receptor levels: a survey of current practice, techniques, and quantitation method”, Blackwell Publishing, The Breast Journal, Volume 6, Number 3, May 2000, pp. 189-196 (8).